Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1
Autor(a) principal: | |
---|---|
Data de Publicação: | 2009 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/jspui/handle/123456789/13456 |
Resumo: | Inflammation has been pointed out as an important factor in development of chronic diseases, as diabetes. Hyperglycemia condition would be responsible by toll-like receptors, TLR2 and TLR4, and, consequently by local and systemic inflammation induction. Thus, the objective of present study was to evaluate type 1 Diabetes mellitus (T1DM) pro-inflammatory state through mRNA expression of TLRs 2 and 4 and proinflammatory cytokines IL-1β, IL-6 and TNF-α correlating to diabetic nephropathy. In order to achieve this objective, 76 T1DM patients and 100 normoglycemic (NG) subjects aged between 6 and 20 years were evaluated. T1DM subjects were evaluated as a total group DM1, and considering glycemic control (good glycemic control DM1G, and poor glycemic control DM1P) and considering time of diagnosis (before achieving 5 years of diagnosis DM1< 5yrs, and after achieving 5 years of diagnosis DM1 <5yrs). Metabolic control was evaluated by glucose and glycated hemoglobin concentrations; to assess renal function serum urea, creatinine, albumin, total protein and urinary albumin-to-creatinine ratio were determined and to evaluate hepatic function, AST and ALT serum activities were measured. Pro-inflammatory status was assessed by mRNA expression of TLRs 2 and 4 and the inflammatory cytokines IL-1β, IL-6 and TNF-α. Except for DM1G group (18.4%), DM1NC patients (81.6%) showed a poor glycemic control, with glycated hemoglobin (11,2%) and serum glucose (225,5 md/dL) concentrations significantly increased in relation to NG group (glucose: 76,5mg/dL and glycated hemoglobin: 6,9%). Significantly enhanced values of urea (20%) and ACR (20,8%) and diminished concentrations of albumin (5,7%) and total protein (13,6%) were found in T1DM patients, mainly associated to a poor glycemic control (DM1P increased values of urea: 20% and ACR:49%, and diminished of albumin: 13,6% and total protein:13,6%) and longer disease duration (DM1 <5yrs - increased values of urea: 20% and ACR:20,8%, and diminished of albumin: 14,3% and total protein:13,6%). As regarding pro-inflammatory status evaluation, significantly increased mRNA expressions were presented for TLR2 (37,5%), IL-1β (43%), IL-6 (44,4%) and TNF-α (15,6%) in T1DM patients in comparison to NG, mainly associated to DM1P (poor glycemic control TLR2: 82%, IL-1β: 36,8% increase) and DM1 <5yrs (longer time of diagnosis TLR2: 85,4%, IL-1β: 46,5% increased) groups. Results support the existence of an inflammatory state mediated by an increased expression of TLR2 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in T1DM |
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Ururahy, Marcela Abbott Galvãohttp://lattes.cnpq.br/8016222352823817http://lattes.cnpq.br/4245215108740331Sales, Valéria Soraya de Fariashttp://lattes.cnpq.br/8525532896559374Hirata, Mario Hiroyukihttp://lattes.cnpq.br/8551642748793896Rezende, Adriana Augusto de2014-12-17T14:16:26Z2011-01-032014-12-17T14:16:26Z2009-03-30URURAHY, Marcela Abbott Galvão. Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1. 2009. 114 f. Dissertação (Mestrado em Bioanálises e Medicamentos) - Universidade Federal do Rio Grande do Norte, Natal, 2009.https://repositorio.ufrn.br/jspui/handle/123456789/13456Inflammation has been pointed out as an important factor in development of chronic diseases, as diabetes. Hyperglycemia condition would be responsible by toll-like receptors, TLR2 and TLR4, and, consequently by local and systemic inflammation induction. Thus, the objective of present study was to evaluate type 1 Diabetes mellitus (T1DM) pro-inflammatory state through mRNA expression of TLRs 2 and 4 and proinflammatory cytokines IL-1β, IL-6 and TNF-α correlating to diabetic nephropathy. In order to achieve this objective, 76 T1DM patients and 100 normoglycemic (NG) subjects aged between 6 and 20 years were evaluated. T1DM subjects were evaluated as a total group DM1, and considering glycemic control (good glycemic control DM1G, and poor glycemic control DM1P) and considering time of diagnosis (before achieving 5 years of diagnosis DM1< 5yrs, and after achieving 5 years of diagnosis DM1 <5yrs). Metabolic control was evaluated by glucose and glycated hemoglobin concentrations; to assess renal function serum urea, creatinine, albumin, total protein and urinary albumin-to-creatinine ratio were determined and to evaluate hepatic function, AST and ALT serum activities were measured. Pro-inflammatory status was assessed by mRNA expression of TLRs 2 and 4 and the inflammatory cytokines IL-1β, IL-6 and TNF-α. Except for DM1G group (18.4%), DM1NC patients (81.6%) showed a poor glycemic control, with glycated hemoglobin (11,2%) and serum glucose (225,5 md/dL) concentrations significantly increased in relation to NG group (glucose: 76,5mg/dL and glycated hemoglobin: 6,9%). Significantly enhanced values of urea (20%) and ACR (20,8%) and diminished concentrations of albumin (5,7%) and total protein (13,6%) were found in T1DM patients, mainly associated to a poor glycemic control (DM1P increased values of urea: 20% and ACR:49%, and diminished of albumin: 13,6% and total protein:13,6%) and longer disease duration (DM1 <5yrs - increased values of urea: 20% and ACR:20,8%, and diminished of albumin: 14,3% and total protein:13,6%). As regarding pro-inflammatory status evaluation, significantly increased mRNA expressions were presented for TLR2 (37,5%), IL-1β (43%), IL-6 (44,4%) and TNF-α (15,6%) in T1DM patients in comparison to NG, mainly associated to DM1P (poor glycemic control TLR2: 82%, IL-1β: 36,8% increase) and DM1 <5yrs (longer time of diagnosis TLR2: 85,4%, IL-1β: 46,5% increased) groups. Results support the existence of an inflammatory state mediated by an increased expression of TLR2 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in T1DMA inflamação tem sido descrita como um fator importante no desenvolvimento de doenças crônicas como o diabetes, e a condição da hiperglicemia seria a responsável pela ativação dos receptores toll-like (TLRs), TLR2 e TLR4, e, conseqüentemente, pela indução da inflamação local e sistêmica. Nesse sentido, o presente estudo teve como objetivo de avaliar o estado pró-inflamatório do Diabetes mellitus tipo 1 (DM1) através da expressão gênica de TLRs 2 e 4 e das citocinas pró-inflamatórias IL-1β, IL-6 e TNF- α, e correlacionar com o desenvolvimento da nefropatia diabética. Foram estudados 76 pacientes diabéticos tipo 1 e 100 indivíduos normoglicêmicos NG, na faixa etária de 6 a 20 anos. Os indivíduos diabéticos foram avaliados como um grupo total DM1, e subdivididos em função do controle glicêmico (diabéticos compensados DM1C, e não-compensados DM1NC) e em função do tempo de diagnóstico (diabéticos com menos de 5 anos de diagnóstico DM1< 5anos, e a partir de 5 anos de diagnóstico DM1 <5 anos). Para a avaliação do controle metabólico foram determinadas as concentrações de glicose e de hemoglobina glicada; para avaliar a função renal as concentrações séricas de uréia, creatinina, albumina, proteína total e a relação albumina/creatinina (RAC) urinária; e para função hepática a atividade sérica de AST e ALT. O estado pró-inflamatório foi avaliado a partir da expressão do mRNA dos TLRs 2 e 4, e das citocinas IL-1β, IL-6 e TNF-α. Com exceção do grupo DM1C (18,4%), os pacientes DM1NC (81,6%) apresentaram um controle glicêmico insatisfatório, com valores de mediana para glicose (225,5mg/dL) e hemoglobina glicada (11,2%) significativamente superiores ao grupo NG (glicose: 76,5mg/dL e hemoglobina glicada: 6,9%). Foram obtidos valores aumentados para a uréia sérica (20%) e RAC urinária (20,8%); e diminuídos para albumina (5,7%) e proteína total (13,6%) nos indivíduos diabéticos; e associados a um controle glicêmico insatisfatório (DM1NC aumento de 20% para uréia e 49% para RAC; e diminuição de 8,6% para albumina e 12,1% para proteína total) e a um maior tempo de diagnóstico (DM1 <5anos aumento de 20% para uréia e 20,8% para RAC; e diminuição de 14,3% para albumina e 13,6% para proteína total). No tocante à avaliação do estado pró-inflamatório, as expressões de mRNA se apresentaram elevadas para TLR2 (37,5%), IL-1β (43%), IL-6 (44,4%) e TNF-α (15,6%) nos indivíduos diabéticos em relação aos NG, sendo principalmente associadas aos grupos DM1NC (controle glicêmico insatisfatório TLR2: 82%, IL-1β: 43% de aumento) e DM1 <5 anos (maior tempo de diagnóstico TLR2: 85,4%, IL-1β: 46,5% de aumento). O conjunto de resultados suporta a existência de um quadro inflamatório mediado pelo aumento da expressão do TLR2 e das citocinas pró-inflamatórias IL-1β, IL-6 e TNF-α no diabetes tipo 1Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporUniversidade Federal do Rio Grande do NortePrograma de Pós-Graduação em Ciências FarmacêuticasUFRNBRBioanálises e MedicamentosDiabetes mellitus tipo 1InflamaçãoTLR2CitocinasNefropatia diabéticaType 1 Diabetes mellitusInflammationTLR2CytokinesDiabetic nephropathyCNPQ::CIENCIAS DA SAUDE::FARMACIAAssociação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNORIGINALAssociacaoReceptorToll-like_Ururahy_2009.pdfapplication/pdf6376152https://repositorio.ufrn.br/bitstream/123456789/13456/1/AssociacaoReceptorToll-like_Ururahy_2009.pdf6d7d86fec335062b8c283cdea3878878MD51AssociacaoReceptorToll-like_Ururahy_2009.pdfAssociacaoReceptorToll-like_Ururahy_2009.pdfapplication/pdf124898https://repositorio.ufrn.br/bitstream/123456789/13456/2/AssociacaoReceptorToll-like_Ururahy_2009.pdf96113ee26e3601b5f9c135c9e9a88ed5MD52TEXTMarcelaAGU_DISSERT.pdf.txtMarcelaAGU_DISSERT.pdf.txtExtracted texttext/plain180219https://repositorio.ufrn.br/bitstream/123456789/13456/11/MarcelaAGU_DISSERT.pdf.txt59d3902bf590033e7d70408629b7fafeMD511MarcelaAGU_DISSERT_PARCIAL.pdf.txtMarcelaAGU_DISSERT_PARCIAL.pdf.txtExtracted texttext/plain20042https://repositorio.ufrn.br/bitstream/123456789/13456/13/MarcelaAGU_DISSERT_PARCIAL.pdf.txtcb16213a42b59ddcb8d6945ea19708c1MD513AssociacaoReceptorToll-like_Ururahy_2009.pdf.txtAssociacaoReceptorToll-like_Ururahy_2009.pdf.txtExtracted texttext/plain180042https://repositorio.ufrn.br/bitstream/123456789/13456/15/AssociacaoReceptorToll-like_Ururahy_2009.pdf.txtfa157a9e5f893aad13360d8638a470abMD515THUMBNAILMarcelaAGU_DISSERT.pdf.jpgMarcelaAGU_DISSERT.pdf.jpgIM Thumbnailimage/jpeg3373https://repositorio.ufrn.br/bitstream/123456789/13456/12/MarcelaAGU_DISSERT.pdf.jpg6220be47989ec99c5d397108bc630f6bMD512MarcelaAGU_DISSERT_PARCIAL.pdf.jpgMarcelaAGU_DISSERT_PARCIAL.pdf.jpgIM Thumbnailimage/jpeg3373https://repositorio.ufrn.br/bitstream/123456789/13456/14/MarcelaAGU_DISSERT_PARCIAL.pdf.jpg6220be47989ec99c5d397108bc630f6bMD514AssociacaoReceptorToll-like_Ururahy_2009.pdf.jpgAssociacaoReceptorToll-like_Ururahy_2009.pdf.jpgGenerated Thumbnailimage/jpeg1437https://repositorio.ufrn.br/bitstream/123456789/13456/16/AssociacaoReceptorToll-like_Ururahy_2009.pdf.jpg6a3b83327bf8c7d710bb25dd78d6e61bMD516123456789/134562019-05-26 02:22:38.205oai:https://repositorio.ufrn.br:123456789/13456Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2019-05-26T05:22:38Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.por.fl_str_mv |
Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1 |
title |
Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1 |
spellingShingle |
Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1 Ururahy, Marcela Abbott Galvão Diabetes mellitus tipo 1 Inflamação TLR2 Citocinas Nefropatia diabética Type 1 Diabetes mellitus Inflammation TLR2 Cytokines Diabetic nephropathy CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1 |
title_full |
Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1 |
title_fullStr |
Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1 |
title_full_unstemmed |
Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1 |
title_sort |
Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1 |
author |
Ururahy, Marcela Abbott Galvão |
author_facet |
Ururahy, Marcela Abbott Galvão |
author_role |
author |
dc.contributor.authorID.por.fl_str_mv |
|
dc.contributor.authorLattes.por.fl_str_mv |
http://lattes.cnpq.br/8016222352823817 |
dc.contributor.advisorID.por.fl_str_mv |
|
dc.contributor.advisorLattes.por.fl_str_mv |
http://lattes.cnpq.br/4245215108740331 |
dc.contributor.referees1.pt_BR.fl_str_mv |
Sales, Valéria Soraya de Farias |
dc.contributor.referees1ID.por.fl_str_mv |
|
dc.contributor.referees1Lattes.por.fl_str_mv |
http://lattes.cnpq.br/8525532896559374 |
dc.contributor.referees2.pt_BR.fl_str_mv |
Hirata, Mario Hiroyuki |
dc.contributor.referees2ID.por.fl_str_mv |
|
dc.contributor.referees2Lattes.por.fl_str_mv |
http://lattes.cnpq.br/8551642748793896 |
dc.contributor.author.fl_str_mv |
Ururahy, Marcela Abbott Galvão |
dc.contributor.advisor1.fl_str_mv |
Rezende, Adriana Augusto de |
contributor_str_mv |
Rezende, Adriana Augusto de |
dc.subject.por.fl_str_mv |
Diabetes mellitus tipo 1 Inflamação TLR2 Citocinas Nefropatia diabética |
topic |
Diabetes mellitus tipo 1 Inflamação TLR2 Citocinas Nefropatia diabética Type 1 Diabetes mellitus Inflammation TLR2 Cytokines Diabetic nephropathy CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Type 1 Diabetes mellitus Inflammation TLR2 Cytokines Diabetic nephropathy |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Inflammation has been pointed out as an important factor in development of chronic diseases, as diabetes. Hyperglycemia condition would be responsible by toll-like receptors, TLR2 and TLR4, and, consequently by local and systemic inflammation induction. Thus, the objective of present study was to evaluate type 1 Diabetes mellitus (T1DM) pro-inflammatory state through mRNA expression of TLRs 2 and 4 and proinflammatory cytokines IL-1β, IL-6 and TNF-α correlating to diabetic nephropathy. In order to achieve this objective, 76 T1DM patients and 100 normoglycemic (NG) subjects aged between 6 and 20 years were evaluated. T1DM subjects were evaluated as a total group DM1, and considering glycemic control (good glycemic control DM1G, and poor glycemic control DM1P) and considering time of diagnosis (before achieving 5 years of diagnosis DM1< 5yrs, and after achieving 5 years of diagnosis DM1 <5yrs). Metabolic control was evaluated by glucose and glycated hemoglobin concentrations; to assess renal function serum urea, creatinine, albumin, total protein and urinary albumin-to-creatinine ratio were determined and to evaluate hepatic function, AST and ALT serum activities were measured. Pro-inflammatory status was assessed by mRNA expression of TLRs 2 and 4 and the inflammatory cytokines IL-1β, IL-6 and TNF-α. Except for DM1G group (18.4%), DM1NC patients (81.6%) showed a poor glycemic control, with glycated hemoglobin (11,2%) and serum glucose (225,5 md/dL) concentrations significantly increased in relation to NG group (glucose: 76,5mg/dL and glycated hemoglobin: 6,9%). Significantly enhanced values of urea (20%) and ACR (20,8%) and diminished concentrations of albumin (5,7%) and total protein (13,6%) were found in T1DM patients, mainly associated to a poor glycemic control (DM1P increased values of urea: 20% and ACR:49%, and diminished of albumin: 13,6% and total protein:13,6%) and longer disease duration (DM1 <5yrs - increased values of urea: 20% and ACR:20,8%, and diminished of albumin: 14,3% and total protein:13,6%). As regarding pro-inflammatory status evaluation, significantly increased mRNA expressions were presented for TLR2 (37,5%), IL-1β (43%), IL-6 (44,4%) and TNF-α (15,6%) in T1DM patients in comparison to NG, mainly associated to DM1P (poor glycemic control TLR2: 82%, IL-1β: 36,8% increase) and DM1 <5yrs (longer time of diagnosis TLR2: 85,4%, IL-1β: 46,5% increased) groups. Results support the existence of an inflammatory state mediated by an increased expression of TLR2 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in T1DM |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-03-30 |
dc.date.available.fl_str_mv |
2011-01-03 2014-12-17T14:16:26Z |
dc.date.accessioned.fl_str_mv |
2014-12-17T14:16:26Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
URURAHY, Marcela Abbott Galvão. Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1. 2009. 114 f. Dissertação (Mestrado em Bioanálises e Medicamentos) - Universidade Federal do Rio Grande do Norte, Natal, 2009. |
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https://repositorio.ufrn.br/jspui/handle/123456789/13456 |
identifier_str_mv |
URURAHY, Marcela Abbott Galvão. Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1. 2009. 114 f. Dissertação (Mestrado em Bioanálises e Medicamentos) - Universidade Federal do Rio Grande do Norte, Natal, 2009. |
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https://repositorio.ufrn.br/jspui/handle/123456789/13456 |
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Universidade Federal do Rio Grande do Norte |
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Programa de Pós-Graduação em Ciências Farmacêuticas |
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UFRN |
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BR |
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Bioanálises e Medicamentos |
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Universidade Federal do Rio Grande do Norte |
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